Accurate methods to probe the structure, conformation and dynamics of biopolymers, as well as their specific noncovalent interactions, are tremendously important for understanding biochemistry at the molecular level. Mass spectrometry has the advantages of high speed, ultrahigh sensitivity (attomole detection), and high specificity (mass accuracy +/- a few Da at >100,000 Da). Tandem mass spectrometry is used for identifying and locating postranslational modifications and binding sites, identifying proteins present in complex mixtures, etc. It is one aim of this proposal to improve the efficiency and extent of backbone fragmentation using electron capture dissociation, and develop this method to obtain information about biopolymer conformation. H/D exchange measurements, both in the gas and solution phase, will be combined with collisional cross section measurements, electron capture dissociation, and molecular dynamics simulations to obtain detailed information about conformation both in solution and in the gas phase. By comparing results in these two different environments, information about the role of solvent on biopolymer conformation can be directly obtained. Another aim is to understand how the structure of an ion changes during the transition from bulk solution to the isolated environment of the gas phase during the electrospray ionization process. It is hoped that by understanding this process, we can relate the structural information of biopolymers and noncovalent complexes determined from gas-phase experiments back to the structures of the ions in bulk solution. Another aim is to understand the role of specific noncovalent interactions and the influence of solvent on these interactions. Noncovalent interactions are important in enzyme-substrate reactivity, supermolecular complex formation and in many diseases, such as prion based diseases including spongiform encephalopathies and CreutzfeldJacob disease.